The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index; none of the 112 sources its claims cite is checked for support yet.
Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder
Open accessAbstract
Major depressive disorder (MDD) is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function. Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials and reduced brain GSH levels. Also, F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms. Urinary excretion of 8-OHdG seems to be higher in patients with MDD compared to healthy controls. Despite the fact that antidepressant drugs have been used for more than 50 years, their mechanism of action is still not fully understood. This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD. Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress. These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes preclinical and clinical evidence that major depressive disorder (MDD) is accompanied by elevated oxidative stress and that antidepressant treatment, especially longer-term, may reduce oxidative stress and augment antioxidant defences. It suggests that augmentation of antioxidant defences may be one mechanism underlying the neuroprotective effects of antidepressants in MDD.
Key findings
- MDD has been associated with lower serum/plasmatic total antioxidant potentials, reduced brain GSH levels, lower plasma coenzyme Q10, increased serum xanthine oxidase, increased F2-isoprostanes correlated with depressive symptom severity, and higher urinary 8-OHdG versus healthy controls.
- In vitro and animal studies mostly support antioxidant-related effects of antidepressants, but some show prooxidant effects at high doses, particularly fluoxetine in rat liver; for example, chronic fluoxetine increased liver TBARS, carbonyl groups, and uric acid, with effects more pronounced at 24 versus 8 mg/kg.
- Clinical studies suggest treatment duration matters: short-term treatments (4 to 8 weeks) do not seem to alter antioxidant/oxidative parameters, whereas longer treatments (12 to 24 weeks) seem to induce robust antioxidant effects.
- Specific clinical findings include restoration of plasmatic GPx and MDA after 12 weeks of SSRIs in 32 MDD patients; in 57 MDD patients, TOS and OSI were higher and TAC lower, with severity correlations of r = 0.58, r = 0.63, and r = −0.553, and after 3 months of treatment TOS/OSI decreased and TAC increased.
Methods
- Narrative review of preclinical (in vitro and animal model), post-mortem, and clinical literature on oxidative/antioxidant effects associated with antidepressant agents in MDD.
- Data include studies summarized in tables, with human cohorts ranging from small samples to 96 MDD patients and treatment durations from 4 to 24 weeks.
- Main analysis is qualitative synthesis of reported oxidative stress markers, antioxidant enzymes, and treatment effects; no systematic search strategy or meta-analysis is described.
Limitations
- The paper states that post-mortem studies are not conclusive mostly because of small sample sizes, lack of control groups, and lack of relevant information such as treatment duration and specific drugs used.
- The paper states that many clinical studies were short in duration and likely underpowered to address differences in antioxidant potential among particular drugs, and that larger studies are warranted.
- The paper notes that peripheral markers may not necessarily correlate with central nervous system changes, citing Teyssier et al. (2011), who found oxidative stress-response genes were not altered in the prefrontal cortex of individuals with MDD, although all patients had received antidepressant treatment. Evident from the text: the review is narrative and heterogeneous across drugs, doses, tissues, and outcome markers, limiting direct comparability.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 112 cited sources checked · 0 supported · 0 flagged
In the paper
“increased serum XO levels observed in MDD subjects suggest increased systemic ROS production [29].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [29] Herken H Gurel A Selek S Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment Archives of Medical Research 2007 38 2 247 252 17227736 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“A recent post-mortem study found increased XO activity in the thalamus and putamen patients with recurrent MDD [35].”
- Also stated in: § 4.3. Post-Mortem Studies · plain
“Michel et al. (2010) showed increased XO activity in the thalamus and putamen of seven individuals with an ante-mortem diagnosis of recurrent MDD (age range = 61–93 y.o.).”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [35] Michel TM Camara S Tatschner T Increased xanthine oxidase in the thalamus and putamen in depression World Journal of Biological Psychiatry 2010 11 2 314 320 20218795 source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § 4.3. Post-Mortem Studies · plain
In the paper
“Plasmatic coenzyme Q10 (CoQ10), a strong antioxidant and a key molecule in the mitochondrial electron transport chain, is significantly lower in major depressive patients [34]”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [34] Maes M Mihaylova I Kubera M Uytterhoeven M Vrydags N Bosmans E Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness Neuroendocrinology Letters 2009 30 4 462 469 20010493
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“urinary excretion of 8-OHdG, a marker of oxidative damage to DNA, was found to be higher in patients with MDD than healthy controls [52].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [52] Maes M Mihaylova I Kubera M Uytterhoeven M Vrydags N Bosmans E Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome Neuroendocrinology Letters 2009 30 6 715 722 20035260
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials [28, 32, 48] and reduced brain GSH levels [31] as compared to matched controls.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [28] Sarandol A Sarandol E Eker SS Erdinc S Vatansever E Kirli S Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems Human Psychopharmacology 2007 22 2 67 73 17299810 source
- Not checked yetcites [32] Cumurcu BE Ozyurt H Etikan I Demir S Karlidag R Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment Psychiatry and Clinical Neurosciences 2009 63 5 639 645 19674383 source
- Not checked yetcites [48] Gałecki P Szemraj J Bieńkiewicz M Florkowski A Gałecka E Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment Pharmacological Reports 2009 61 3 436 447 19605942 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Findings from animal models and in vitro studies about antidepressant antioxidant effects are relevant to human MDD treatment.
- Rests on an assumption: Peripheral markers of oxidative stress (serum/plasmatic) reflect central/brain oxidative stress in MDD.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Findings from animal models and in vitro studies about antidepressant antioxidant effects are relevant to human MDD treatment.
- Rests on an assumption: Peripheral markers of oxidative stress (serum/plasmatic) reflect central/brain oxidative stress in MDD.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Findings from animal models and in vitro studies about antidepressant antioxidant effects are relevant to human MDD treatment.
- Rests on an assumption: Peripheral markers of oxidative stress (serum/plasmatic) reflect central/brain oxidative stress in MDD.
In the paper
“Kolla et al. (2005) have demonstrated that pretreatment with amitriptyline and fluoxetine protects against oxidative stress-induced damage in rat pheochromocytoma (PC12) cells.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.1. Studies In Vitro
What the sources say
- Not checked yetcites [10] Kolla N Wei Z Richardson JS Li XM Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide Journal of Psychiatry and Neuroscience 2005 30 3 196 201 15944744 PMC1089780
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Both drugs attenuated the decrease in cell viability induced by H2O2 in PC12 cells.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.1. Studies In Vitro
What the sources say
- Not checked yetcites [10] Kolla N Wei Z Richardson JS Li XM Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide Journal of Psychiatry and Neuroscience 2005 30 3 196 201 15944744 PMC1089780
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 24
- Probably not a substantial claim. 2
- The quote only partly states this claim. 2
None of the sources cited for this claim have been checked yet.
In the paper
“The pathophysiology of depression is multifactorial and includes changes in brain monoaminergic transmission (e.g., 5-HT, NE, DA), abnormalities in neurotransmitter receptors function (e.g., AC-cAMP pathway), reduced neurotrophic factors (e.g., BDNF), dysregulation of HPA axis (cortisol), increased proinflammatory cytokines (e.g., IL-6, TNF-α, NF-κB), increased NO (e.g., L-arginine-NO-cGMP pathway”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [45] Coyle JT Puttfarcken P Oxidative stress, glutamate, and neurodegenerative disorders Science 1993 262 5134 689 695 7901908 source
- Not checked yetcites [46] Gardner A Boles RG Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 3 730 743 20691744 source
- Not checked yetcites [47] Chopra K Kumar B Kuhad A Pathobiological targets of depression Expert Opinion on Therapeutic Targets 2011 15 4 379 400 21254923 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Dimopoulos et al. (2008) have found that F2-isoprostanes (F2-iso) circulatory levels were increased in major depressive patients and were significantly correlated with the severity of depressive symptoms [50].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 3. Oxidative Stress in Major Depressive Disorder
What the sources say
- Not checked yetcites [50] Dimopoulos N Piperi C Psarra V Lea RW Kalofoutis A Increased plasma levels of 8-iso-PGF2α and IL-6 in an elderly population with depression Psychiatry Research 2008 161 1 59 66 18783834 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“These results suggest that imipramine treatment may induce changes in substrate oxidation pattern, increase rate of ATP synthesis, and can potentially increase mitochondrial ROS production.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [20] Katyare SS Rajan RR Effect of long-term in vivo treatment with imipramine on the oxidative energy metabolism in rat brain mitochondria Comparative Biochemistry and Physiology Part C 1995 112 3 353 357 8838689
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“High dose (10 mg/kg) of venlafaxine, however, decreased the intensity of BDNF immunostaining in all subareas of the hippocampus and increased the intensity of Cu/Zn-SOD immunostaining in the dentate granular cell layer [21].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [21] Xu H Steven Richardson J Li XM Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus Neuropsychopharmacology 2003 28 1 53 62 12496940 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Souza et al. (1994) reported that fluoxetine may be potentially hepatotoxic at high doses [7].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.1. Studies In Vitro
What the sources say
- Not checked yetcites [7] Souza MEJ Polizello ACM Uyemura SA Castro-Silva O Curti C Effect of fluoxetine on rat liver mitochondria Biochemical Pharmacology 1994 48 3 535 541 8068040 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“low dose (5 mg/kg) of amitriptyline and venlafaxine increased the intensity of BDNF immunostaining in hippocampal pyramidal neurons and the intensity of Bcl-2 immunostaining in hippocampal mossy fibers, but did not alter the Cu/Zn-SOD immunoreactivity.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [21] Xu H Steven Richardson J Li XM Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus Neuropsychopharmacology 2003 28 1 53 62 12496940 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“At all doses tested, venlafaxine decreased MDA and total nitrite levels, increased total antioxidant potential and GSH content, and restored GST activity in hippocampus of stressed animals.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [26] Abdel-Wahab BA Salama RH Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice Pharmacology Biochemistry and Behavior 2011 100 1 59 65 21835191 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Nahon et al. (2005) demonstrated that fluoxetine was able to inhibit the opening of the mitochondrial permeability transition (MPT) pore, the release of cytochrome c (cytC) and protected against staurosporine-induced apoptotic cell death [8].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.1. Studies In Vitro
What the sources say
- Not checked yetcites [8] Nahon E Israelson A Abu-Hamad S Shoshan-Barmatz V Fluoxetine (Prozac) interaction with the mitochondrial voltage-dependent anion channel and protection against apoptotic cell death FEBS Letters 2005 579 22 5105 5110 16139271 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Venlafaxine also promoted increased total antioxidant potential and GSH levels in the control, nonstressed group.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [26] Abdel-Wahab BA Salama RH Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice Pharmacology Biochemistry and Behavior 2011 100 1 59 65 21835191 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Control animals and stressed animals displayed decreased activity of SOD and increased activity of GPx.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [25] Djordjevic J Djordjevic A Adzic M Elaković I Matić G Radojcic MB Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver European Journal of Pharmacology 2011 659 1 61 66 21414309 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
In the paper
“Djordjevic et al. (2011) showed altered antioxidant status and increased apoptotic signalling in male rat liver after 21 days of fluoxetine treatment.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [25] Djordjevic J Djordjevic A Adzic M Elaković I Matić G Radojcic MB Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver European Journal of Pharmacology 2011 659 1 61 66 21414309 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, imipramine treatment increased brain creatine kinase and increased activity of mitochondrial respiratory chain complexes [18, 53].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [18] Reus GZ Stringari RB Gonçalves CL Administration of harmine and imipramine alters creatine kinase and mitochondrial respiratory chain activities in the rat brain Depression Research and Treatment 2012 2012 7 pages Article ID 987397. PMC3182396 21969912
- Not checked yetcites [53] Reus GZ Stringari RB Rezin GT Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain Journal of Neural Transmission 2012 119 4 481 491 21953515 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one), a substance that mimics the activity of the antioxidant enzyme GPx [56], decreased immobility time in rodents, an effect that was dependent on its interaction with the noradrenergic and dopaminergic systems [57].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [57] Posser T Kaster MP Baraúna SC Rocha JBT Rodrigues ALS Leal RB Antidepressant-like effect of the organoselenium compound ebselen in mice: evidence for the involvement of the monoaminergic system European Journal of Pharmacology 2009 602 1 85 91 19026628 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In rats displaying depressive-like behaviour induced by chronic mild stress, administration of liquiritin, an antioxidant derived from Glycyrrhiza uralensis, decreased immobility time, increased sucrose consumption, increased SOD activity, and attenuated MDA production in the peripheral blood [55].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [55] Zhao Z Wang W Guo H Zhou D Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis in chronic variable stress induced depression model rats Behavioural Brain Research 2008 194 1 108 113 18655806 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In a subsequent study with the same cohort, GST levels were also reduced in MDD patients and no effects of antidepressant treatment were observed [36].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.3. Post-Mortem Studies
What the sources say
- Not checked yetcites [36] Gawryluk JW Wang JF Andreazza AC Shao L Yatham LN Young LT Prefrontal cortex glutathione S-transferase levels in patients with bipolar disorder, major depression and schizophrenia The International Journal of Neuropsychopharmacology 2011 14 8 1069 1074 21733244 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, a major limitation of the studies above mentioned is that not all studies measured oxidative stress markers (i.e., MDA, carbonyl); therefore, these prooxidant effects need further investigation.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“No differences in locomotor activity were observed, suggesting a selective antidepressant-like effect.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 4. Antioxidant Effects of Antidepressants > 4.2. Animal Models
What the sources say
- Not checked yetcites [54] Rojas P Serrano-García N Medina-Campos ON Pedraza-Chaverri J Ögren SO Rojas C Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in the mouse forced swimming test: role of oxidative stress Neurochemistry International 2011 59 5 628 638 21672588 source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Plasmatic MDA, serum oxidized LDL (OxLDL) levels, and erythrocyte SOD activity were increased in MDD patients before treatment”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 5. Clinical Data: Human Studies
What the sources say
- Not checked yetcites [33] Kotan VO Sarandol E Kirhan E Ozkaya G Kirli S Effects of long-term antidepressant treatment on oxidative status in major depressive disorder: a 24-week follow-up study Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 5 1284 1290 21515329 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“there is also evidence suggesting that BDNF, oxidative stress, and inflammation tend to be abnormal among individuals with multiple mood episodes and correlate with length of illness [51, 66, 67].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 6. Concluding Remarks
What the sources say
- Not checked yetcites [51] Praticò D Rokach J Lawson J FitzGerald GA F2-isoprostanes as indices of lipid peroxidation in inflammatory diseases Chemistry and Physics of Lipids 2004 128 1-2 165 171 15037161 source
- Not checked yetcites [66] Frey BN Zunta-Soares GB Caetano SC Illness duration and total brain gray matter in bipolar disorder: evidence for neurodegeneration? European Neuropsychopharmacology 2008 18 10 717 722 18554875 source
- Not checked yetcites [67] Minuzzi L Behr GA Moreira JCF Frey BN Mitochondrial dysfunction in bipolar disorder: lessons from brain imaging and molecular markers Revista Colombiana de Psiquiatría 2011 40 166 182 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Considering that the presence of oxidative (and nitrosative) stress may cause neurodegeneration and reduced neurogenesis [63, 64]”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 6. Concluding Remarks
What the sources say
- Not checked yetcites [63] Maes M Ruckoanich P Chang YS Mahanonda N Berk M Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 3 769 783 20561554 source
- Not checked yetcites [64] Maes M Galecki P Chang YS Berk M A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 3 676 692 20471444 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, in this post-mortem study all of the patients had received antidepressant treatment, which may have normalized oxidative stress parameters.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 6. Concluding Remarks
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Also, SOD activity was increased in patients with MDD, and there was a positive correlation between the severity of depressive symptoms and SOD activity (r = 0.419).”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 5. Clinical Data: Human Studies
What the sources say
- Not checked yetcites [28] Sarandol A Sarandol E Eker SS Erdinc S Vatansever E Kirli S Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems Human Psychopharmacology 2007 22 2 67 73 17299810 source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In this study, MDD patients had increased plasmatic MDA levels and increased susceptibility of red blood cells (RBCs) to oxidation.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 5. Clinical Data: Human Studies
What the sources say
- Not checked yetcites [28] Sarandol A Sarandol E Eker SS Erdinc S Vatansever E Kirli S Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems Human Psychopharmacology 2007 22 2 67 73 17299810 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Furthermore, the authors found a positive correlation between the severity of the disease and serum TOS and OSI (r = 0.58, and r = 0.63, resp.).”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 5. Clinical Data: Human Studies
What the sources say
- Not checked yetcites [32] Cumurcu BE Ozyurt H Etikan I Demir S Karlidag R Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment Psychiatry and Clinical Neurosciences 2009 63 5 639 645 19674383 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
In the paper
“Before treatment, MDD patients displayed increased erythrocyte SOD and CAT activities, increased MDA levels, and decreased plasmatic total antioxidant status (TAS) level.”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 5. Clinical Data: Human Studies
What the sources say
- Not checked yetcites [48] Gałecki P Szemraj J Bieńkiewicz M Florkowski A Gałecka E Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment Pharmacological Reports 2009 61 3 436 447 19605942 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Treatment with citalopram (20 mg/day, n = 10), fluoxetine (20 mg/day, n = 11), fluvoxamine (150 mg/day, n = 7), or sertraline (50 mg/day, n = 8) for 8 weeks increased SOD activity whereas decreased XO levels”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 5. Clinical Data: Human Studies
What the sources say
- Not checked yetcites [29] Herken H Gurel A Selek S Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment Archives of Medical Research 2007 38 2 247 252 17227736 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“They concluded that the pathogenic role of oxidative stress in the neurobiology of depression could not be inferred from alterations in the periphery [65].”
§ Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder > 6. Concluding Remarks
What the sources say
- Not checked yetcites [65] Teyssier JR Ragot S Chauvet-Gélinier JC Trojak B Bonin B Expression of oxidative stress-response genes is not activated in the prefrontal cortex of patients with depressive disorder Psychiatry Research 2011 186 2-3 244 247 20800905 source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
Findings from animal models and in vitro studies about antidepressant antioxidant effects are relevant to human MDD treatment.
“This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD.”
The paper relies on this without support.
Peripheral markers of oxidative stress (serum/plasmatic) reflect central/brain oxidative stress in MDD.
“Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials [28, 32, 48] and reduced brain GSH levels [31] as compared to matched controls.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“it was shown that the mood stabilizers and antidepressant therapies possess high antioxidant potential [115].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [115]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Sex counts exceed the stated cohort size
MinorThe stated female and male counts sum to 36, not 20. The four treatment-group counts later in the same cohort also sum to 36.
Reported 20 · recomputed 36
“Decreased serum SOD and increased XO were found in 20 individuals with MDD (age range 17–62 years, 19/17 F/M ratio) [29].”
Citations
Cites
Ellman, G. L. (1959) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(59)90090-6 · Cited by 26,824
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,526
Oxidative Stress, Glutamate, and Neurodegenerative Disorders
Coyle, J. T., & Puttfarcken, P. (1993) · Science · doi:10.1126/science.7901908 · Cited by 3,762
Rio, D. D., Stewart, A. J., & Pellegrini, N. (2005) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2005.05.003 · Cited by 2,789
Janero, D. R. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90131-2 · Cited by 2,735
Oxidative stress and neurodegeneration: where are we now?
Halliwell, B. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03907.x · Cited by 2,614
Protein carbonyl groups as biomarkers of oxidative stress
Dalle‐Donne, I., Rossi, R., Giustarini, D., Milzani, A., & Colombo, R. (2003) · Clinica Chimica Acta · doi:10.1016/s0009-8981(03)00003-2 · Cited by 2,352
Biochemistry of oxidative stress
Halliwell, B. B. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351147 · Cited by 1,591
Cellular Defenses against Superoxide and Hydrogen Peroxide
Imlay, J. A. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061606.161055 · Cited by 1,563
Flagged first, then by citations
Research works printed but not linked: 5
- 2005, Journal of Psychiatry and Neuroscience, 30, 196
- 2012, Depression Research and Treatment, 2012
- 1995, Comparative Biochemistry and Physiology Part C, 112, 353
- 2009, Neuroendocrinology Letters, 30, 462
- 2009, Neuroendocrinology Letters, 30, 715
Cited by
Sorted by citations
Items 201–206 of 206
Arora, A., Vacy, K., Marques, C., Degeratu, M.-O., Mastropasqua, F., Humphrey, J., Ye, X., Oksanen, M., Vuillermin, P., Ponsonby, A., et al. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106291 · Cited by 1
Eldaweny, A. M., Yahia, S., Sayed, R. H., Abdelaziz, A. I., & El-sherbiny, I. M. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108583
Hussein, N., Elsabbagh, R. A., El-Bahy, A. A. Z., Handoussa, H., & Abdel-Maksoud, S. M. (2026) · Pharmacological Research - Natural Products · doi:10.1016/j.prenap.2026.100794
Antidepressants, mood-stabilizing drugs, and mitochondrial function: For better or for worse
Preston, G. J., Sabbagh, D. E. S. E., Emmerzaal, T. L., Morava, É., Andreazza, A. C., Rahman, S., & Kozicz, T. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45078-5.00040-3
BindingDB Entry 50021197: Selenization of Small Molecule Drugs: A New Player on the Board.
BindingDB (2025) · UC San Diego · doi:10.7270/q2m331cq
Pervaiz, S., Cattane, N., & Cattaneo, A. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.107064
Metadata
- Authors
- Behr, G. A., Moreira, J. C. F., & Frey, B. N.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- McMaster University (CA)
- Corresponding author
- Behr, Guilherme A.
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2012
- Volume
- 2012
- Pages
- 1-13
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC3368202
- OpenAlex
- W1977657096
- Semantic Scholar
- 8844560d54d30597299b29b489c8ee918eb74996
- Cited by
- 205
- References
- 69
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 16 · 2023: 10 · 2022: 14 · 2021: 12 · 2020: 18 · 2019: 10 · 2018: 12 · 2017: 20 · 2016: 17 · 2015: 24 · 2014: 17 · 2013: 16 · 2012: 3
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BEX 5383/10-2)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- major depressive disorder, antidepressants, antioxidant activity, oxidative stress, glutathione, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, oxidative DNA damage, neuroprotection, antioxidant defense, antidepressant mechanism
- MeSH terms
- Animals, Antidepressive Agents, Antioxidants, Brain, Clinical Trials as Topic, Major Depressive Disorder, Depressive Disorder, Major, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Oxidative Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
